Download Possible heart failure associated with pregabalin use

AĞRI 2011;23(2):80-83
CASE REPORT - OLGU SUNUMU
doi: 10.5505/agri.2011.35119
Possible heart failure associated with pregabalin use:
case report
Pregabalin kullanımı sonrası gelişen muhtemel kalp yetmezliği:
Olgu sunumu
Gülay ERDOĞAN,1 Dilek CEYHAN,2 Sacit GÜLEÇ2
Summary
Pregabalin and gabapentin are widely used analgesic, anticonvulsant and anxiolytic agents as they are relatively reliable and
easily tolerated. However, they may cause some side effects such as dizziness, somnolence, dose-dependent peripheral edema,
and weight gain, which may cause patients to abandon their use. Furthermore, there are a few reports in the literature addressing elderly patients with serious chronic disease and cardiac history, who develop heart failure during pregabalin application.
In this report, we present a patient with no cardiac history treated with 300 mg/kg pregabalin due to neuropathic pain, who
developed peripheral and then central edema, which were determined after advanced investigations. After stopping pregabalin, the situation regressed. Then, peripheral edema developed associated with the recommended dose of gabapentin, which
was used in place of pregabalin. Despite the lack of any published evidence, the New York Heart Association issued a warning about using caution when prescribing pregabalin to type III-IV heart failure patients. Though the effect mechanisms of
pregabalin and gabapentin are not well known, the calcium channel relationship may lead to these side effects. In summary, we
believe that pregabalin and gabapentin, which is mostly used nowadays, should be administered with care not only in patients
with advanced cardiac pathology but also in all patients, due to the potential side effects.
Key words: Heart failure; edema; pregabalin.
Özet
Pregabalin ve gabapentin, göreceli güvenilirlikleri ve kolay tolere edilebilmeleri nedeniyle kullanım alanı giderek genişleyen antikonvülzan, analjezik ve anksiyolitik ajanlardır. Buna karşı, baş dönmesi, somnolans, doz bağımlı periferik ödem ve kilo artışı gibi yan
etkileri ilaç kesilmesine neden olabilmektedir. Ayrıca, literatürde ciddi kronik hastalık öyküsü ve kardiyak öyküsü olan yaşlı hastalarda kalp yetmezliği geliştiğine dair az sayıda olguya rastlanmıştır. Bu yazıda, kardiyak öyküsü olmayan ve nöropatik ağrı nedeniyle 300 mg/gün pregabalin sonrası öncelikle periferik ödem ve sonrasında ileri tetkiklerde tespit edilen santral ödem tablosu gelişen bir hasta sunuldu. Pregabalin kesilmesi sonrası tablonun gerilediği gözlenmekle birlikte önerilen dozlarda başlanan gabapentinle
de periferik ödem gelişmiştir. New York Kalp Cemiyeti sınıf III-IV kalp yetmezliği olan hastalarda pregabalin reçete edilirken dikkatli olunması konusunda uyarmıştır. Etki mekanizmaları henüz netlik kazanmamış olmakla birlikte kalsiyum kanalları üzerindeki etkileri bu yan etkilerle ilişkili olabilir. Sonuç olarak, giderek artan hızda kullanılan bu ilaçların yan etkiler açısından ileri kardiyak hastalar dışında da yakından takip edilmesi gerektiği kanaatindeyiz.
Anahtar sözcükler: Kalp yetmezliği; ödem; pregabalin.
Department of Anaesthesiology and Reanimation, Inonu University Faculty of Medicine, Malatya;
Department of Anaesthesiology and Reanimation, Osmangazi University Faculty of Medicine, Eskisehir, Turkey
1
İnönü Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Malatya;
2
Osmangazi Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Eskişehir
1
2
Submitted - July 14, 2010 (Başvuru tarihi - 14 Temmuz 2010)
Accepted after revision - November 1, 2010 (Düzeltme sonrası kabul tarihi - 1 Kasım 2010)
Correspondence (İletişim): Gülay Erdoğan, M.D. İnönü Üniversitsi Tıp Fakültesi Turgut Özal Tıp Merkezi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Malatya, Turkey.
Tel: +90 - 422 - 341 06 60 / 3119 e-mail (e-posta): [email protected]
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NİSAN - APRIL 2011
Possible heart failure associated with pregabalin use
Introduction
Pregabalin and gabapentin are similar compounds
with analgesic, anticonvulsant and anxiolytic characteristics. Owing to such pharmacological features,
they are commonly used throughout the world in
neuropathic pain treatment and anxiety disorders.
[1]
In addition to these, the number of publications
reporting their use in other areas such as postoperative analgesia and fibromyalgia is also on the rise.[2,3]
Many comprehensive and randomized controlled
studies of high quality have shown the reliability
and efficiency of pregabalin and gabapentin in neuropathic pain treatment, thus making them the first
option in such treatment. The greatest advantages
of these drugs have been listed as their relative reliability, easy use, high tolerance, and lack of negative
interaction with other drugs.[1]
Slight and moderate side effects, such as dizziness
and somnolance, in central nervous system are major factors for terminating the use of pregabalin. At
the same time in some studies dose dependent usage
of pregabalin induced peripheral edema and weight
gain in 5-20 % and 4-12 % of patients, respectively.
[4]
Moreover, few studies have also reported a possible association between pregabalin use and chronic
heart failure decompensation.[4-6] This article presents a case of heart failure after pregabalin use, despite the existence of previous cardiac history.
Case Report
A-54-year-old female patient presented to our Pain
Clinic with a burning sensation and back pain.
Her back pain had started after the bilateral thoracic sympathectomy in which she had undergone
2 months before, advanced through the left arm,
and was continuous and strong. In the physical examination, incision scar at left thoracotomy and allodynia at 3rd and 4th thoracic dermatomes were
identified. The patient reported to have used nonsteroidal anti-inflammatory drugs against pain but
did not achieve any outcome. In addition, she did
not have any previous history of a chronic disease
or medication; was recommended inhaler salbutamol for short-term dyspnea only in the postoperative stage; and had stopped using it when the need
disappeared.
NİSAN - APRIL 2011
Together with these findings, she was diagnosed as
intercostal neuralgia and initially approached to have
a medical treatment. The treatment started with 150
mg/day pregabalin for first week, continued with
300 mg/day in the second week. The starting dose
of tramadol 37.5 mg/day was increased gradually;
and a follow-up was recommended 2 weeks later.
The patient came for follow-up on 17th day of treatment and reported swelling in hands and ankles
which started 3 days ago. During extremity examination, 2 positive pretibial edema was determined.
The patient was admitted to the Pain Clinic for the
side effect follow-up and pain palliation. The peripheral edema was initially attributed to pregabalin and the usage of drug was stopped. The blood
examination showed that electrolyte, blood urea
nitrogen and creatinine levels were within normal
limits and glomerular filtration speed was 86.88 ml/
min/1.73. For the continuing pain, tramadol was
given via patient-controlled analgesia (PCA) (bolus 6 mg, lock-out time 10 min, 4 hr limit 60 mg).
After determining daily tramadol requirement, oral
tramadol retard 100 mg was added to the analgesic
medication, and PCA was stopped on day 3. On
follow up, hemodynamic parameters were stable. In
addition, inhaler salbutamol was given again for the
occasional slight dyspnea. At the end of one week,
the patient was discharged with pain palliation, reduced peripheral edema, and tramadol retard 200
mg/daily medication. After discharge, she was recommended to visit the Internal Medicine Polyclinic
for follow-up.
The patient was examined by thorax computed tomography scan (CT), which was requested by the
Internal Medicine Polyclinic. According to that,
cardiomegalia, appearance of pericardial fluid, additionally pleural fluid at the base of both hemithorax even more significant on the right were revealed.
After CT results only diuretic treatment has begun
and in the third day of treatment echocardiography
results showed 76% ejection fraction and no pathological findings other than pleural effusion. In the
follow-up thorax CT performed 15 days after stopping pregabalin, cardiomegalia and pericardial fluid
had disappeared and only minimal pleural effusion
was seen. Peripheral edema had regressed and the
complaint of dyspnea had disappeared.
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AĞRI
The patient reported reduced but persisting pain,
upon which 300 mg/day gabapentin started and
was increased to 900 mg/day with close follow-up.
However, due to the edema that developed approximately 20 days later, gabapentin was stopped and
analgesia was achieved only with tramadol. The edema due to gabapentin was also followed up closely
and regressed on day 3.
Discussion
In our patient peripheral edema developed on 14th
day of treatment with 300 mg/day pregabalin. Since
no other chronic disease history and medication
were present to explain the peripheral edema, pregabalin was initially held responsible and stopped
to use. Due to the existing postoperative story of
the patient, we did not associate dyspnea with this
picture initially. Upon the lack of an abnormality
in hemodynamic parameters and kidney function
tests, and the regression in peripheral edema, we
did not require further examinations or treatment.
However, the thorax CT led to the conclusion that
pregabalin causes central as well as peripheral edema. The lack of a cardiac etiological factor corroborated our view.
The side effects of pregabalin was investigated by using Naranjo algorithm. Accordingly, the drug scored
7 on the Naranjo algorithm and accepted as having
potential side effects.[7]
A few case reports have claimed an association between pregabalin and chronic heart failure decompensation.[4-6] Unlike to our patient, those reported
in these studies had low ejection fraction and multiple chronic disease histories classified as stage II-III
in the New York Heart Association classification.
Page et al. has reported the possible association between pregabalin administration and chronic heart
failure decompensation in their 3 separate cases. In
one of their cases, they used 600 mg/day gabapentin instead of pregabalin and reported an improvement on patients neuropathy without worsening of
clinical status.[4] However, gabapentin is claimed to
induce peripheral and central edema with doses exceeding 1800 mg/day, and caution is recommended
when it is used instead of pregabalin in the chronic
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pain treatment of patients with heart failure.[8,9] As
our patient did not favor interventional methods
and had persistent complaints, we administered gabapentin under close follow-up and increased the
dose according to patient response. However, peripheral edema was observed during the third week
of 900 mg/day gabapentin treatment.
American Food and Drug Administration has issued a warning about hypotension and peripheral
edema that pregabalin may cause, particularly when
used in combination with thiazolidinedione. Further, despite the presence of any published evidence,
NYHA also issued a warning about being careful
when prescribing it to type III-IV heart failure patients.[10] No such warning has been issued by the
European Medications Evaluation Agency.
The effect mechanisms of pregabalin and gabapentin are not well known. Previous studies claimed
that they show their analgesic effects by binding to
α2-δ type 1 and 2 subunits of voltage dependent
the calcium channels and by reducing potassium
dependent the calcium entry. The effects of α2-δ
type 1 and 2 subunits on calcium channel functions
and conventional calcium channel subtypes are not
clear.[11] Stefani et al. assert that gabapentin may affect L-type calcium channels.[12] This calcium channel relationship may lead to peripheral edema with
peripheral vasodilation and fluid leak into the interstitial area. It is thought that quick and unexplained
weight gain may be a sign of fluid retention, which
may exacerbate congestive heart failure.[13,14]
In this case report, we presented the development
of heart failure in a patient without previous cardiac
pathology after normal dose pregabalin use. In summary, we believe that pregabalin, which is mostly
used nowadays, should be administered with care
due to its potential side effects, and in cases of edema or heart failure associated with pregabalin use,
gabapentin should be considered under caution.
References
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